The Cardiovascular Effects of Sevoflurane and Isoflurane After Premedication of Healthy Dogs Undergoing Elective Surgery
Sevoflurane and isoflurane are commonly used in veterinary anesthesia. The objective of this prospective, randomized, open-label clinical study was to compare the cardiovascular effects of sevoflurane and isoflurane via direct arterial blood pressure measurements and the lithium dilution cardiac output (LDCO) on premedicated healthy dogs undergoing elective tibial plateau leveling osteotomy (TPLO). Nineteen client-owned dogs were included. All dogs were premedicated with hydromorphone (0.05 mg/kg IV and glycopyrrolate 0.01 mg/kg subcutaneously). Ten dogs were anesthetized with sevoflurane and nine dogs were anesthetized with isoflurane. Eighteen dogs were instrumented with a dorsal pedal arterial catheter, and one dog had a femoral arterial catheter. All dogs had continuous, direct systolic (SAP), diastolic (DAP), and mean arterial (MAP) blood pressure readings as well as heart rate (HR), cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI), stroke volume variation (SVV), and pulse pressure variation (PPV) recorded q 5 min during the surgical procedure. There was no significant statistical difference in all parameters between the sevoflurane and isoflurane treatment groups. Both sevoflurane and isoflurane inhalant anesthetics appear to have similar hemodynamic effects when used as part of a multimodal anesthetic protocol in premedicated healthy dogs undergoing an elective surgical procedure.
Introduction
Sevoflurane and isoflurane are inhalant anesthetics commonly used for general anesthesia in veterinary medicine.1 Sevoflurane has a smaller blood:gas partition coefficient (0.68 versus 1.46) and a higher minimum alveolar concentration (MAC) than isoflurane (2.36% versus 1.30% in dogs).1 Those characteristics indicate that sevoflurane is less potent than isoflurane, but may result in more rapid induction and recovery.2
In human patients, blood pressure response to changes in inspired concentrations of sevoflurane are more rapid than isoflurane, and sevoflurane is associated with a more stable and lower heart rate (HR) compared with isoflurane at comparable MACs.2–5 Both inhalant anesthetics maintain cardiac output (CO) at similar levels.2–4
When comparing the speed and quality of induction of general anesthesia using sevoflurane and isoflurane in dogs, variable results have been shown.6,7 Multiple studies found that dogs anesthetized with sevoflurane had a better quality of recovery compared with dogs anesthetized with isoflurane, but with similar recovery times.8,9 Using a cross-over design, Lopez et al. (2009) found no difference in quality of recovery, but found that sevoflurane resulted in a shorter time to standing than isoflurane in dogs induced with propofol.10 Although not the main focus of their study, those investigators also noted that the sevoflurane group had significantly higher systolic arterial blood pressure (SAP), diastolic arterial blood pressure (DAP), and mean arterial blood pressures (MAPs) at various time points after induction. In a different study, when using a mask induction and maintenance of anesthesia in dogs, sevoflurane was found to have a higher anesthetic index than isoflurane, which suggests that sevoflurane has a higher margin of safety.11 In other words, the ratio of units of sevoflurane anesthetic required for adequate anesthetic depth as compared with the number of units that produce either respiratory or cardiovascular depression was found to be higher than isoflurane.
Despite the data in research animals, there are limited investigations that compare the cardiovascular effects of sevoflurane and isoflurane when used as part of a balanced anesthetic protocol in clinical patients. The objective of this study was to describe the cardiovascular effects of sevoflurane anesthesia and isoflurane anesthesia in healthy dogs undergoing elective tibial plateau leveling osteotomy (TPLO). The authors hypothesized that healthy premedicated dogs receiving sevoflurane for maintenance of anesthesia would have fewer hypotensive events, require fewer clinical interventions to treat hypotension or inappropriate anesthetic depth, and have less depression of CO than dogs receiving isoflurane anesthesia.
Materials and Methods
Inclusion Criteria
Animals included in the study were healthy male and female dogs weighing ≥ 10 kg and ≤ 10 yr old that presented to the Veterinary Specialty Hospital for elective TPLO. Dogs were deemed healthy by physical examination and routine blood work (i.e., complete blood cell count and serum biochemical analysis).
Exclusion Criteria
Patients were excluded if they had a previously diagnosed coagulopathy, known metabolic or endocrine disease, or pulmonary disease. Dogs with heart murmurs on physical exam had an echocardiogram performed by a board-certified cardiologist and were excluded if they were found to have clinically significant cardiac disease. Dogs were also excluded if they were currently receiving corticosteroids, acepromazine or other sedatives, drugs for treatment of cardiac disease, or drugs and supplements known to affect blood pressure.
Owner consent was obtained after the study was discussed in person by a study investigator (J.A. or F.P.) and a consent form was signed. The study was approved by the Veterinary Specialty Hospital Animal Care and Use Committee.
Study Design
This was a prospective, randomized, open-label study with two treatment groups. Randomization was performed using a computerized randomizing programa.
To calibrate the lithium dilution cardiac output (LDCO) monitor b, a plasma Na level was measured on the day of surgery using a point of care analyzerc,d in addition to packed cell volume and total plasma solids by refractometry. Anesthetic protocol for all dogs included placement of either a right or left cephalic 18 gauge 1” cathetere and premedication with hydromorphonef (0.05 mg/kg IV) and glycopyrrolateg (0.01 mg/kg subcutaneously) 30–60 min prior to anesthetic induction. Anesthesia was induced with diazepamh (0.25 mg/kg IV) and propofoli (2–4 mg/kg IV to effect). Based on randomization, anesthesia was maintained with sevofluranej (treatment group one) or isofluranek (treatment group two) at 1.5 × MAC (end-tidal inhalant targets: sevoflurane 3.5% and isoflurane 2%) during the course of the procedure unless significant hypotension, decreases in CO, or increased depth of anesthesia was observed as described below. An O2 flow rate of 2–3 L/min was used. The multiagent monitor was calibratedl prior to the start of the study and end-tidal inhalant concentrations were measured at the wye piece of the anesthesia circuitm. Despite patient premedication protocol, a higher MAC of 1.5 was chosen to minimize the number of interventions required for inadequate depth of anesthesia and associated fluctuations in cardiovascular parameters. IV isotonic crystalloidn was administered to all patients at a rate of 10 mL/kg/hr throughout the procedure. Once anesthetized, either a 20 gauge or 22 gauge 1" catheter was placed in the dorsal pedal artery of the opposite pelvic limb from the operative site. One dog had a 20 gauge 1" femoral arterial catheter placed because placement into the dorsal pedal artery was not successfully achieved. All dogs were placed on a mechanical ventilatoro with tidal volumes between 10 mL/kg and 15 mL/kg and a respiratory rate adjusted to maintain an end-tidal carbon dioxide concentration between 35 mm Hg and 45 mm Hg. The anesthetist was not blinded as to which inhalant was being delivered.
Depth of anesthesia during the procedure was monitored via jaw tone, eye position, and palpebral reflex and was characterized as light, medium, or deep according to a standardized scale.12 A medium plane of anesthetic depth was targeted for all patients.
After induction, the arterial catheter was connected to an arterial pressure transducerp and a multiparameter monitorq and zeroed according to the manufacturer’s recommendations. The LDCO machine was calibrated using lithium dilution two times according to the manufacturer’s instructions and previous publication.13,14 It was used for continuous monitoring of: CO, cardiac index (CI), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI), stroke volume (SV), MAP, pulse pressure variation (PPV), stroke volume variation (SVV), and HR.13 Direct SAP and DAP; indirect SAP, DAP, and MAP; inspired and expired inhalant concentrations; end-tidal CO2 and O2 saturation by pulse oximetryq were also recorded q 5 min throughout the length of the surgical procedure. Inhalant concentrations were measured continuously from the endotracheal tube wye piece.
Intervention was deemed to be necessary when two subsequent direct arterial blood pressure measurements 5 min apart were at least 10 mm Hg below the lower end of the normal range SAP of ≤ 90 mm Hg or MAP of ≤ 70 mm Hg. If either PPV or SVV were > 10% as continuously calculated by the LDCO monitor for a period of 10 min, animals were administered a 10 mL/kg crystalloid bolus IV.
The following interventions were performed in the following order at 5 min intervals if the patient was or continued to be hypotensive:
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End-tidal inhalant concentration was decreased by 0.5%.
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End-tidal inhalant concentration was decreased by another 0.5%.
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10 mL/kg crystalloid bolus was administered IV over 10 min.
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Another 10 mL/kg crystalloid bolus was administered IV over 10 min.
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End-tidal inhalant concentration was further decreased by 0.5%.
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5 ml/kg hetastarchr bolus was administered IV over 10 min.
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Another 5 mL/kg hetastarch bolus was administered IV over 10 min.
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An IV constant rate infusion of dopamines was started at 5 μg/kg/min. If additional vasopressor support was required, the patient was removed from the study.
If a dog was deemed to be at a light plane of anesthesia based on several combined parameters such as elevated heart, central eye position, palpebral reflex present, lack of ventilator/patient synchrony, and/or purposeful movement, a dose of propofol was given IV to effect (total dose administered ranged from 2 mg/kg to 4 mg/kg). Propofol was chosen as a rescue anesthetic because it is quick acting and short lasting and allowed other changes in anesthetic protocol to then be subsequently performed. Once the dog was in a medium plane of anesthesia, the end-tidal inhalant concentration was then increased by 0.5% to maintain that plane of anesthesia once the effect of propofol had dissipated.
Hemodynamic and respiratory values were recorded during surgical preparation and throughout surgery. Baseline values were recorded 5 min prior to the start of surgery. The start of surgery and TPLO time points were also noted. Once surgery was completed, the arterial catheter was removed and data collection was terminated. Preservative free morphinet 0.1 mg/kg was administered via epidural injection after postoperative radiographs were taken and hydromorphone 0.075 mg/kg IV was administered upon extubation. The authors’ normal protocol is to administer epidural analgesia prior to surgery; however, for the purpose of this study, the epidural was administered postoperatively prior to extubation.
Statistical Analysis
Statistical analysis was performed using commercially available statistics programsu,v. Normality was assessed using the Kolmogorov-Smirnov test. Baseline cardiovascular and descriptive parameters were compared between groups using unpaired Student t tests or Mann-Whitney tests as appropriate for the data distribution. Within drug groups, change over time was assessed using an analysis of variance (ANOVA) for repeated measures or the Friedman test for repeated measures ANOVA on ranks. Because of the variability between individual durations of anesthesia as well as the timing of events (e.g., TPLO), a two-way ANOVA was not used to compare drug groups. For each patient and parameter in each inhalant group, the area under the curve for the total values was calculated. Those areas under the curve were then compared as a group between drug treatments using unpaired Student t tests or Mann-Whitney tests as appropriate for the data distribution. Discrete episodes such as hypotension were compared using χ2 analysis. The number of episodes of intervention involving a decrease in inhalant, a fluid bolus, a propofol bolus, or an increase in inhalant was evaluated by a Fisher exact test. Finally, in an attempt to assess patient response to a standard stimulus, parameters from 5 min before, during, and after the tibial osteotomy were compared using repeated measures ANOVA or Friedman repeated measures ANOVA on ranks. If the osteotomy lasted longer than one 5 min period, the “during” category was derived from an average of the two time periods while the osteotomy was occurring. Normally distributed data were described as mean ± standard deviation and nonparametric data were described as median (range).
Results
Nineteen dogs were studied, including eight castrated males, nine spayed females, one male, and one female. Body weights ranged from 10 kg to 60.9 kg (median, 33.4 kg) and ages ranged from 1 yr to 9.5 yr (median, 5 yr). Table 1 summarized the composition of both treatment groups. The average surgery time for all dogs was 60.1 min ± 9 min (sevoflurane, 60 min ± 9 min; isoflurane, 60.1min ± 10 min) and there were no differences between groups for age, weight, or duration parameters (age, P = 0.812; weight, P = 0.732; duration, P = 0.98).
SD, standard deviation.
There was no significant change in either end-tidal isoflurane or end-tidal sevoflurane for the duration of the study (P = 0.161 and P = 0.779, respectively, Figure 1). When all dogs were considered, the highest average end-tidal isoflurane occurred at 15 min into the surgery and was 1.813 ± 0.247% and the lowest value occurred at the start of anesthesia (t = 0) and was 1.475 ± 0.191%. The highest average end-tidal sevoflurane occurred at t = 5 and was 3.10 ± 0.488%. The lowest end-tidal sevoflurane value occurred at t = 50 min and was 2.92 ± 0.416%. After 55 min, the end-tidal sevoflurane and isoflurane concentrations were not different between the two groups, but not all dogs were evaluated. For sevoflurane, four dogs were evaluated at 60 min and 65 min and two dogs were evaluated at 70 min and 75 min. For isoflurane, four dogs were evaluated at 60 min and 65 min and one dog was evaluated at 70 min.
![FIGURE 1. Plot of end-tidal inhalant concentrations (mean ± standard deviation [SD]) over time during the course of an elective orthopedic surgical procedure in dogs anesthetized with either sevoflurane (n = 10) or isoflurane (n = 9). For sevoflurane, four dogs were evaluated at 60 min and 65 min and two dogs were evaluated at 70 min and 75 min. For isoflurane, four dogs were evaluated at 60 min and 65 min and one dog was evaluated at 70 min. Overall, there was no significant difference in inhalant concentration between groups.](/view/journals/aaha/50/1/27fig1.jpeg)
![FIGURE 1. Plot of end-tidal inhalant concentrations (mean ± standard deviation [SD]) over time during the course of an elective orthopedic surgical procedure in dogs anesthetized with either sevoflurane (n = 10) or isoflurane (n = 9). For sevoflurane, four dogs were evaluated at 60 min and 65 min and two dogs were evaluated at 70 min and 75 min. For isoflurane, four dogs were evaluated at 60 min and 65 min and one dog was evaluated at 70 min. Overall, there was no significant difference in inhalant concentration between groups.](/view/journals/aaha/50/1/full-27fig1.jpeg)
![FIGURE 1. Plot of end-tidal inhalant concentrations (mean ± standard deviation [SD]) over time during the course of an elective orthopedic surgical procedure in dogs anesthetized with either sevoflurane (n = 10) or isoflurane (n = 9). For sevoflurane, four dogs were evaluated at 60 min and 65 min and two dogs were evaluated at 70 min and 75 min. For isoflurane, four dogs were evaluated at 60 min and 65 min and one dog was evaluated at 70 min. Overall, there was no significant difference in inhalant concentration between groups.](/view/journals/aaha/50/1/inline-27fig1.jpeg)
Citation: Journal of the American Animal Hospital Association 50, 1; 10.5326/JAAHA-MS-5963
When evaluated in terms of MAC multiples, few dogs reached the target of 1.5 × MAC (Figure 2). There was no difference in MAC multiple between dogs receiving either isoflurane or sevoflurane at any time point (P = 0.788). The highest average MAC multiple in the isoflurane group (1.39 ± 0.2) was reached 15 min into the procedure, and the highest average MAC multiple in the sevoflurane group (1.31 ± 0.2) was reached 5 min into the procedure.
Citation: Journal of the American Animal Hospital Association 50, 1; 10.5326/JAAHA-MS-5963
Cardiovascular Parameters
Baseline HR values did not vary significantly between groups (P = 0.396; Table 2). Average HR did not change significantly during surgery for dogs in either the isoflurane or sevoflurane groups (P = 0.094 and P = 0.244, respectively). There was no significant difference in HR between groups (P = 0.801) during surgery. Baseline values for blood pressure parameters were listed in Table 2. SAP was not significantly different between groups at baseline (P = 0.738) and did not vary significantly during surgery for either group (isoflurane, P = 0.651; sevoflurane, P = 0.604). The same was true of MAP (baseline comparison, P = 0.779; isoflurane, P = 0.651; sevoflurane, P = 0.604) and DAP (baseline comparison, P = 0.800; isoflurane, P = 0.651; sevoflurane, P = 0.604). Area under the curve for all blood pressure measurements failed to show significant differences between groups (SAP, P = 0.536; MAP, P = 0.940; DAP, P = 0.764).
CI, cardiac index; CO, cardiac output; DAP, diastolic arterial blood pressure; HR, heart rate; MAP, mean arterial blood pressure; PPV, pulse pressure variation; SAP, systolic arterial blood pressure; SD, standard deviation; SV, stroke volume; SVR, systemic vascular resistance; SVRI, systemic vascular resistance index; SVV, stroke volume variation.
There were no differences between the sevoflurane and isoflurane group for baseline CO, CI, SVR, SV, SVRI, SVV, or PPV (Table 2). CO and CI did not vary significantly with time in either group (CO sevoflurane, P = 0.679; CO isoflurane, P = 0.994; CI sevoflurane, P = 0.332; CI isoflurane, P = 0.995). SVR and SVRI likewise did not vary with time (SVR sevoflurane, P = 0.998; SVR isoflurane, P = 0.999; SVRI sevoflurane, P = 0.280; SVRI isoflurane, P = 0.392, Table 2). SV did not vary with time in either group (isoflurane, P = 0.676; sevoflurane, P = 0.725). SVV did not vary significantly with time in either group (isoflurane, P = 0.312; sevoflurane, P = 0.817). PPV did not vary significantly with time in either group (isoflurane, P = 0.731; sevoflurane, P = 0.869).
There were no statistical differences between inhalants with regard to any measured LDCO parameters throughout the duration of anesthesia (CO, P = 0.725; CI, P = 0.621; SVR, P = 0.838; SV, P = 0.975; SVRI, P = 0.910; SVV, P = 0.744; PPV, P = 0.957).
There were 10 instances of hypotension in the isoflurane group and 4 in the sevoflurane group (P = 0.096). There were 14 interventions resulting in a decrease in the end-tidal inhalant concentration in the isoflurane group and 16 in the sevoflurane group (P = 0.2836). Nine of 10 dogs required at least one decrease in end-tidal inhalant concentration in the sevoflurane group, 5 of which occurred in a single dog. Eight of nine dogs in the isoflurane group required at least one decrease. There was one intervention of an IV bolus of crystalloid in the isoflurane group and two in the sevoflurane group (P = 1). There were five episodes of additional propofol use in the isoflurane group and one in the sevoflurane group (P = 0.213). Those results have been summarized in Table 3.
The end-tidal inhalant concentration was increased nine times in the isoflurane group in seven individual dogs. End-tidal inhalant concentration was increased only five times in the sevoflurane group in four individual dogs (P = 1). Those results were also summarized in Table 3.
When evaluating changes in cardiovascular parameters immediately before, during, and after the osteotomy, significant changes were only seen in SVR and PPV. The SVR in the isoflurane group increased from 1,600.6 dynes × sec/cm ± 749 dynes × sec/cm before the osteotomy to 1,920 dynes × sec/cm ± 1,060 dynes × sec/cm after the osteotomy (P = 0.012). The SVR for dogs anesthetized with sevoflurane decreased from 1,826.1 dynes × sec/cm ± 1,228 dynes × sec/cm to 1,786.9 dynes × sec/cm ± 1,018 dynes × sec/cm (P = 0.086). PPV was also significantly increased in the isoflurane group from before the osteotomy to after (9.9% ± 4% to 15.4% ± 9%, P = 0.027). The corresponding values in the sevoflurane group decreased from a median value of 13% (range, 7–90%) to a median of 11% (range, 1–16%; P = 0.378). When PPV was sustained above 10% for more than 10 min, intervention with a crystalloid bolus was inconsistently given. There were no statistically significant changes in either inspired sevoflurane or isoflurane concentrations throughout the anesthetic period (sevoflurane, P = 0.887; isoflurane, P = 0.307; Figure 1).
Discussion
In this study, there were no statistical differences between the effect of sevoflurane and isoflurane administered at equipotent doses on intraoperative HR, SAP, DAP, MAP, CO, SVR, SV, CI, SVRI, PPV, or SVV. The premedication, induction drugs, and both inhalants provided a hemodynamically stable anesthetic period for healthy patients undergoing TPLO, evidenced by the lack of difference between the incidence of hypotension and number of interventions. The significant changes seen in SVR and PPV in the isoflurane group during the tibial osteotomy were likely a sympathetic response to surgical stimulation. The lack of change in the sevoflurane group and the fewer propofol interventions needed in that group may indicate either a more stable or deeper anesthetic plane in the sevoflurane group.
Torri et al. (2000) investigated cardiovascular hemodynamics between healthy adult humans anesthetized with either sevoflurane or isoflurane.15 Noninvasive blood pressure and HR were similar in both groups. Cardiovascular side effects seen in both treatment groups included hypotension (SAP decrease > 30% baseline), bradycardia (HR < 50 beats/min), and tachycardia (HR > 100 beats/min); however, those were deemed clinically insignificant. There were no statistical differences between groups in the number of episodes. Interestingly, when this study group was stratified for age, more hemodynamic side effects were seen in patients > 50 yr of age in the isoflurane group (29.1% versus 15.2%, respectively).15 Hypotension was the most common side effect seen and was hypothesized to occur due to a more profound depressant effect on baroreceptor activity produced by isoflurane, resulting in a greater decrease in peripheral resistance than sevoflurane.15 As there was a wide age range in this study and relatively few dogs studied, a comparison using age stratification would be underpowered and was not performed. The maintenance of an increased SVR seen with sevoflurane in older patient populations may merit further investigation.
In this study, the authors found no statistically significant difference in HR and blood pressure between the two anesthetic inhalants administered at equipotent doses. Polis et al. (2001) studied the effects on HR, noninvasive arterial blood pressure, and recovery times of 1.5 × and 2 × MAC of sevoflurane, isoflurane, and halothane in dogs.16 Similar to this study, there was no statistically significant difference in HR between sevoflurane and isoflurane at either anesthetic concentration. Likewise, there were no specific differences observed between SAP, DAP, or MAP between the two inhalant groups.
In this study, SVR and SVRI were consistently higher in the sevoflurane group compared with the isoflurane group; however, that observation was not statistically significant. Sevoflurane has been shown to have limited vasodilatory effects in dogs.17 At 0.5 × and 1 × MAC, a decrease in arterial tone was noted, whereas no further effect was seen at 1.5 × MAC. The authors concluded that observed episodes of hypotension were more likely due to decreases in CO rather than arteriolar dilatation.17
No difference in CO was found between sevoflurane and isoflurane. In another study, dogs were anesthetized with pentobarbital and maintained with either sevoflurane (n = 9) or isoflurane (n = 8) and compared with controls, who received no inhalant anesthesia. Sevoflurane significantly decreased HR, left ventricular systolic pressure, CO, rapid ventricular filling rate, and atrial filling rate. Isoflurane produced similar significant decreases in left ventricular systolic pressure, contractility, CO, rapid filling rate, and atrial filling rate.18 The differences between inhalants could not be directly compared in that study because they were administered at the same percent concentrations rather than the same MAC.
Multiple studies in veterinary medicine have shown that LDCO is a reliable, minimally invasive, and accurate way to measure CO in dogs, cats, and horses for single intermittent measurements using lithium chloride.19–24 The mechanism and theory of LDCO analysis has been reported elsewhere.20 The pulse contour analysis cardiac outputw (PCACO) system calculates continuous beat-to-beat CO by analyzing the arterial blood pressure waveform, and is initially calibrated using the LDCO machine.25 A more advanced monitoring systemb combines the LDCO and PCACO systems into one machine and calculates systolic pressure variation, PPV, CI, SV, SV index, SVV, SVR, and SVRI.25 Studies have shown good correlation between this duel monitoring system and other accepted methods of CO measurement.26–28 PPV and SVV are measures of preload, and increased variation suggests inadequate circulating blood volume. When those values are > 11% and > 9.5%, respectively, in human patients, decreases in CO may be volume responsive.29,30 The combined LDCO and PCACO monitoring system does require the use of intermittent positive-pressure ventilation to reduce fluctuations in intrathoracic pressure. The limitation of intermittent positive-pressure ventilation is that it causes increased intrathoracic pressure and decreases CO by compressing major blood vessels and decreasing venous return.31
Despite the veterinary research that shows good correlation between LDCO and thermodilution CO methods in dogs, there are limited studies evaluating the agreement between LDCO and continuous arterial pressure waveform analysis.19 Evidence exists in the human literature that shows good correlation between the two CO measures in patients undergoing cardiac surgery.28 In conscious dogs with systemic inflammatory response syndrome, there was not an acceptable agreement between the LDCO and PCACO at all measured time points, potentially due to changes in either intravascular volume or vascular tone.32 The first measured time point of that study was 4 hr after initial calibration. It is unknown at what time point prior to 4 hr after initial lithium calibration that the LDCO and PCACO stopped having strong agreement with each other. It is possible that there was significant agreement between the LDCO and the PCACO in the beginning of the study. In the current study, the duration of measured values was 60.1 min ± 9 min after initial calibration with lithium, well below the 4 hr mark. Recommended recalibration requirements for the duel monitoring system are once q 24 hr.13 Because the average length of the current study was approximately 60 min, recalibration was not performed.
A study comparing LDCO values to PCACO values following severe hemorrhagic shock in dogs found that the PCACO was not as accurate as the LDCO for detecting either rapid decreases in CO or the effects of fluid resuscitation.33 Those authors concluded that recalibration of the PCACO system may be necessary after any suspected changes in preload. Another study in anesthetized dogs found that CO measurements between the LDCO and PCACO systems did not differ significantly, except when the dogs were in a deep plane of anesthesia (1.5 × MAC), dopamine was administered at adjusted doses IV, or dopamine was administered at 7 μg/kg/min IV.21 Because the study population included in the current study did not undergo any major blood loss or aggressive fluid resuscitation, deep planes of anesthesia were avoided, and vasopressors were not used, recalibration was not performed.
At all recorded time points in this study, there was no statistical difference between HR and there was no trend for a higher HR in one treatment group versus the other. However, those results may be somewhat skewed by the use of glycopyrrolate in this study. Glycopyrrolate, commonly used as part of premedication in clinical patients, is an anticholinergic medication with a 2–3 hr duration of action.34 The maintenance of HR in this study may have been a direct effect of the anticholinergic rather than an effect of either the sevoflurane or isoflurane. In another study, where an anticholinergic was not used as a premedication in dogs anesthetized with either sevoflurane or isoflurane, a significant difference between HR was also not found between the two inhalants.9
In the study by Bennett et al. (2008), similar to the current study, arterial blood pressure measurements also showed no difference between the two treatment groups.9 The current study also used the use of preanesthetic analgesic medications, as appropriate for clinical use. The analgesic effects of hydromorphone may have also blunted the sympathetic response to surgical intervention.
There were several limitations to this study. The small number of cases did not provide adequate statistical power to demonstrate significant differences in CO, HR, blood pressure, and the other measured parameters between groups. A priori power analysis determined an appropriate study number of 10 dogs/group to identify a difference in MAP of 10 mm Hg. That was based on published studies that used single-agent anesthetic protocols. A posthoc power analysis looking at values of SVRI calculated that evaluation of 25 dogs in each group would be necessary to identify significant differences in SVRI, if differences did indeed exist.
The inclusion of premedication and induction drugs allowed lower doses of inhalant to be used, but may have blunted some cardiovascular responses that would have been seen at higher doses of inhalant. Along the same lines, if this study had been performed in premedicated animals that were hemodynamically unstable, differences in the interplay of inhalant anesthetics with the cardiovascular system may have been identified. In healthy, client-owned animals, it was necessary to meet standards of care for analgesia and anesthesia during this study, including the maintenance of appropriate hemodynamics.
Although guidelines were set in place, anesthetic depth was assessed subjectively by the anesthetist and thus inappropriate numbers of interventions, either too few or too many, may have occurred. The anesthetist was also not blinded as to which inhalant anesthetic was used, and thus there may have been inherent bias.
Although the subjects included in this study did not undergo either any major blood loss or fluid resuscitation, recalibration of the duel LDCO and PCACO machine may have been necessary during the times of changed SVR and PPV with osteotomy because the veterinary literature is lacking in supportive evidence that the LDCO and PCACO strongly correlate with one another. Along those same lines, one of the reasons why no differences in measured parameters in both groups were identified may be due to the fact that this advanced monitor may not be as sensitive in detecting such changes as it is in humans. Further veterinary studies utilizing this particular cardiac output monitor are warranted.
Conclusion
Sevoflurane and isoflurane appear to have similar hemodynamic effects in healthy dogs undergoing an elective surgical procedure using a balanced anesthetic protocol. When directly comparing the two inhalants, there does not seem to be a significant difference between using sevoflurane compared with isoflurane when anesthetizing healthy patients. It is not clear if the similarity in cardiovascular stability would be maintained in animals with either hemodynamic instability or critical illness.
Plot of end-tidal inhalant concentrations (mean ± standard deviation [SD]) over time during the course of an elective orthopedic surgical procedure in dogs anesthetized with either sevoflurane (n = 10) or isoflurane (n = 9). For sevoflurane, four dogs were evaluated at 60 min and 65 min and two dogs were evaluated at 70 min and 75 min. For isoflurane, four dogs were evaluated at 60 min and 65 min and one dog was evaluated at 70 min. Overall, there was no significant difference in inhalant concentration between groups.
Plot of minimum alveolar concentration (MAC) multiple (mean ± SD) over time during the course of an elective orthopedic surgical procedure in dogs anesthetized with either sevoflurane (n = 10) or isoflurane (n = 9). The sevoflurane treatment group is depicted by the gray columns, and the isoflurane treatment group is represented by the black columns. No significant differences were found in MAC multiple between inhalant groups at any time point.
Contributor Notes
J. Abed’s present affiliation is the Department of Critical Care, Red Bank Veterinary Hospital, Tinton Falls, NJ.
